Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

UTILISATION DU PAMIDRONATE DANS LE TRAITEMENT DU SYNDROME DE SAPHO (DES RHUMATOLOGIE)

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

LES IMMUNOGLOBULINES POLYVALENTES INTRAVEINEUSES SONT-ELLES EFFICACES DANS LA POLYARTHRITE RHUMATOIDE ? (DES RHUMATOLOGIE)

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Key Indexing Terms: POLYARTERITIS NODOSA VISCERAL HEMATOMA Personal, non-commercial use only

P e r s o n a l n o n -c o m m e r c i a l u s e o n l y . T h e J o u r n a l o f R h e u m a t o l o g y . C o p y r i g h t © 2 0 0 4 . A l l r i g h t s r e s e r v e d The Paris, Cochin Hospital, Paris, France; and Department of Rheumatology, Bulgarian Medical Academy, Sofia, Bulgaria. Y. Allanore, MD; C. Rosenberg, MD, Department of Rheumatology; O. Vignaux, MD, PhD; P. Legmann, MD, PhD, Department of Radiology, Cochin Hospital; K. Kanev, MD, Rheumatology Clinic, Bulgarian Medical Academy; C.J. Menkes, MD; A. Kahan, MD, PhD, Department of Rheumatology, Cochin Hospital. Address reprint requests to Dr. Y. Allanore, Hôpital Cochin, Service de Rhumatologie A, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. E-mail: [email protected] Submitted December 29, 2003; revision accepted March 24, 2004. Polyarteritis nodosa (PAN) is a rare disease characterized by necrotizing vasculitis of small and medium size arteries 1 . The clinical symptoms that usually reveal PAN are neuritis, arthralgia, myalgia, cutaneous lesions, orchitis, and abdominal pain 2 . Prompt diagnosis is important because PAN can be life-threatening: severe organ manifestations include congestive heart failure, cerebrovascular events, gastrointestinal (GI) tract hemorrhage, and malignant hypertension. We describe a patient with an unusual presentation of PAN, revealed by successive spontaneous visceral hematomas involving the kidneys, bladder, and liver. CASE REPORT A 28-year-old Bulgarian man was admitted to our department for exploration of repeated spontaneous hematomas. Symptoms began in March 2000, with isolated, violent lumbar pain, and no decline in general health status. Ultrasound and computed tomography (CT) scans revealed a left perinephritic hematoma. Surgery was performed. Pathological analysis confirmed the diagnosis and identified no other abnormality. The pain disappeared with standard analgesic treatment, and he resumed all regular activities. One year later, he suffered the same symptoms, with right kidney involvement, and the same course. In June 2001, he suffered spontaneous bleeding of the bladder, as revealed by macroscopic hematuria, with no renal insufficiency. This bleeding stopped spontaneously within a few days. One year later, he reported spontaneous pain in the right upper abdominal quadrant, and CT scan revealed the presence of a hematoma in the liver. Investigations over this 2-year period revealed no coagulation or immunological abnormalities, but biological examinations showed repeated signs of transient inflammation with increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Histological analysis of a kidney sample removed during surgery revealed no inflammatory disease, specific infiltration, or vessel abnormalities other than hematoma. By the time of admission to our hospital in March 2003, our patient had lost 20 kg over 2 years (weight 58 kg; height 1.75 m); he had had fever and abdominal pain for 4 days. On physical examination, he was pale and sweating. His blood pressure was 130/80 mm Hg, pulse 100/min, and temperature 38.8°C. Diffuse tenderness was noted on abdominal pressure, without palpable abnormality. Neurological and cardiopulmonary examinations were normal. Laboratory investigations gave the following results: white blood cell count 14,000/mm 3 , ESR 74 mm/h, CRP 240 mg/l (normal < 5 mg/l), hemoglobin concentration 12.6 g/dl, aspartate aminotransferase 402 IU/l, alanine aminotransferase 648 IU/l, creatininemia 67 µmol/l, and absence of proteinuria. Hemostasis test results: prothrombin time 104%, activated partial thromboplastin time 40 s (normal = 40 ± 5), lupus anticoagulant absent; and factor VIII, IX, and von Willebrand levels were normal. Blood cultures, urinalysis, and tests for tuberculosis (skin test and gastric culture), human immunodeficiency virus, hepatitis C virus, and hepatitis B virus (last generation ELISA tests) were negative. No autoantibodies, including antinuclear, anti-dsDNA, antiphospholipid, antiextractible nuclear antigens, antineutrophil cytoplasmic antibodies, rheumatoid factor, or cryoglobulinemia were detected. Thoracic and abdominal radiographs, electrocardiogram, and echocardiography results were normal. Thoracoabdominal CT scan showed 2 recent intrahepatic hematomas, visible as spontaneous hyperdensity lesions DISCUSSIO

N-terminal pro-brain natriuretic peptide is a strong predictor of mortality in systemic sclerosis

Objectives: Cardiovascular involvement is a major contributor to mortality in systemic sclerosis (SSc). We examined whether N-terminal pro-brain natriuretic peptide (NT-proBNP) is a reliable predictor of mortality in SSc. Methods and results: This multicentre prospective cohort study included 523 patients presenting with SSc, whose mean age was 54 +/- 13 years, mean disease duration 8 +/- 9 years, and diffuse cutaneous form in 168. Plasma NT-proBNP was measured at baseline and the patients were followed yearly. Overall mortality was measured at 3 years. At baseline, cardiovascular involvement was present in 37 patients, including 17 with pulmonary artery hypertension (PAH) and 20 with a left ventricular ejection fraction (LVEF) <55%. At 3 years, 32 (7%) patients had died. The median [25th-75th percentile] NT-proBNP concentration was 203 ng/l [129-514] in patients who died within 3 years, versus 88 ng/l [47-167] in survivors (P < 0.001). NT-proBNP was an independent predictor of 3-years mortality in multivariate analysis (P = 0.046). The optimal cut-off derived from the ROC curve was 129 ng/l; sensitivity and specificity to predict 3 y mortality were 78.1 and 66.7%. Using the previously recommended 125-ng/l concentration as threshold value, NT-proBNP reliably and independently predicted 3 year mortality, with a sensitivity of 78.1 and a negative predictive value of 97.6%, respectively (P = 0.006). The consideration of SSc patients without PAH or LVEF < 55% at baseline yielded similar results. Conclusion: NT-proBNP appears as a reliable and independent predictor of mortality in patients with SSc. (C) 2016 Elsevier Ireland Ltd. All rights reserved